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How different hematopoietic and non-hematopoietic cell types interpret these signals is a reflection of cellular context and function. For example, neurons are often viewed as immunologically inert and have muted responses to IFNs. However, because neurons can be targeted by several classes of pathogens, there is a need for these cells to sense infection and respond to IFNs to engage anti-microbial activities. This review discusses the unique features of neuronal IFN signaling, emphasizing how JAK-STAT pathway engagement and downstream induction of interferon-stimulated genes (ISGs) shape intrinsic and extrinsic neuronal anti-pathogen defense.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag169","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T09:40:34Z","timestamp":1782898834000},"source":"Crossref","is-referenced-by-count":1,"title":["Getting on your last nerve: IFNs and resistance to infection"],"prefix":"10.1093","volume":"215","author":[{"given":"Molly E","family":"Bunkofske","sequence":"first","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"2026063015302985200_vkag169-B1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1098\/rspb.1957.0048","article-title":"Virus interference. 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